作者@article {Simpson1901761 = {Cathe辛普森rine E. and Chen, Jenny Y. and Damico, Rachel L. and Hassoun, Paul M. and Martin, Lisa J. and Yang, Jun and Nies, Melanie and Griffiths, Megan and Vaidya, R. Dhananjay and Brandal, Stephanie and Pauciulo, Michael W. and Lutz, Katie A. and Coleman, Anna W. and Austin, Eric D. and Ivy, Dunbar D. and Nichols, William C. and Everett, Allen D.}, title = {Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension}, volume = {55}, number = {4}, elocation-id = {1901761}, year = {2020}, doi = {10.1183/13993003.01761-2019}, publisher = {European Respiratory Society}, abstract = {The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p\<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95\% CI 1.08{\textendash}1.38; p\<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.Circulating IL-6, a pro-inflammatory cytokine produced by pulmonary arterial smooth muscle cells, is significantly associated with clinical phenotypes and survival in pulmonary arterial hypertension, which may guide individualised disease management https://bit.ly/3awkkSz}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/55/4/1901761}, eprint = {//www.qdcxjkg.com/content/55/4/1901761.full.pdf}, journal = {European Respiratory Journal} }